Volume 7 Issue 1, January 2023

Fluorophenols can be activated towards S_NAr reactions by forming a transient electron-withdrawing phenoxyl radical.

Twenty five years ago, Christopher Lipinski and colleagues published arguably the most influential sentence in small-molecule drug discovery. Their cleverly crafted ‘rule of 5’ (Ro5) mnemonic was adopted into everyday medicinal chemistry practice and has influenced a generation of small-molecule drug discovery scientists. Five times five years later, we consider the impact of the Ro5 and ask to what extent it should still guide today’s medicinal chemistry efforts.

The interactions of lipid bilayer cell membranes with liquid biomolecular condensates are key to many biological processes, including endocytosis. New research shows a model system of liposomes that are able to engulf droplets, effectively mimicking endocytosis.

Optical and electrochemical sensing techniques have been used to detect real-time chemical signals in living plants in response to biotic and abiotic stress. Through modelling of data, pathogenic infection of plants can be identified and predicted.

The kinetics resulting from catalyst inhibition can be confused with reactions involving two catalytic species reacting together. This Review highlights common misconceptions, offers advice and good practices to avoid potential pitfalls, and provides critical analyses of 100 literature examples.

Stereochemical editing is a strategy to access three-dimensional skeletons, where the stereochemistry-defining steps are decoupled from the major connectivity-forming reactions. This Review highlights recent advances in the area of light-driven contra-thermodynamic stereochemical editing.

Mechanochemistry is the science of inducing a chemical reaction through the application of mechanical force. This Perspective focuses on combining traditional mechanochemistry with different energy inputs — heat, light, sound or electrical impulses — to advance mechanochemical synthesis.